Aaron Joshua Astalos

Proteasome Inhibitor MG-132 and PKC-ι-Specific Inhibitor ICA-1S Degrade Mutant p53 and Induce Apoptosis in Ovarian Cancer Cell Lines

Ovarian cancer is the most lethal gynecological cancer, with a 5-year survival rate of approximately 50%. Mutation in the p53 gene and overexpression of the atypical protein kinase C iota (PKC-ι) are two phenomena widely manifested in ovarian cancer. This study investigated the role of PKC-ι-specific inhibitor ICA-1S and proteasome inhibitor MG-132 in ovarian cancer cell lines. To discern the result, cell proliferation assays, cytotoxicity assays, Western blotting, immunofluorescence, flow cytometry, small interfering RNA, and co-immunoprecipitation techniques were applied. ICA-1S and MG-132 were found to inhibit the proliferation of ovarian cancer cell lines significantly. ICA-1S reduced the level of oncogenic PKC-ι as expected. In addition, ICA-1S and MG-132 both were able to decrease the level of mutated p53 in the ES-2 cell line through separate pathways. On the contrary, MG-132 increased the level of wild-type p53 in the HEY-T30 cell line by inhibiting proteasomal degradation. MG-132 also induced apoptosis and autophagy in the ovarian cancer cell lines. We concluded that ICA-1S alone or in combination with MG-132 could be a potential treatment for mutated p53-containing and PKC-ι-overexpressing ovarian cancers.